483 research outputs found

    Varietal differences in protein polymer built-up of wheat at different temperature and nitrogen regimes during grain filling

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    Both radionuclide imaging and near-infrared fluorescent (NIRF) imaging have a high sensitivity to detect tumors in vivo. The combination of these modalities using dual-labeled antibodies may allow both preoperative and intraoperative tumor localization and may be used in image-guided surgery to ensure complete resection of tumor tissue. Here, we evaluated the potential of dual-modality imaging of prostate cancer with the monoclonal antibody D2B, directed against an extracellular domain of prostate-specific membrane antigen (PSMA). For these studies, D2B was labeled both with (111)In and with the NIRF dye IRDye800CW.D2B was conjugated with N-hydroxysuccinimide-IRDye800CW and p-isothiocyanatobenzyl-diethylenetriaminepentaacetic acid (ITC-DTPA) and subsequently radiolabeled with (111)In. For biodistribution and NIRF imaging, (111)In-DTPA-D2B-IRDye800CW (2 Όg, 0.55 MBq/mouse) was injected intravenously into BALB/c nude mice with subcutaneous PSMA-expressing LNCaP tumors (right flank) and PSMA-negative PC3 tumors (left flank). The biodistribution was determined at 1, 2, 3, and 7 d after injection. In addition, micro-SPECT/CT and NIRF imaging with (111)In-DTPA-D2B-IRDye800CW (3 Όg, 8.5 MBq/mouse) was performed on mice with intraperitoneally growing LS174T-PSMA tumors.(111)In-DTPA-D2B-IRDye800CW specifically accumulated in subcutaneous PSMA-positive LNCaP tumors (45.8 ± 8.0 percentage injected dose per gram at 168 h after injection), whereas uptake in subcutaneous PSMA-negative PC3 tumors was significantly lower (6.6 ± 1.3 percentage injected dose per gram at 168 h after injection). Intraperitoneal LS174T-PSMA tumors could be visualized specifically with both micro-SPECT/CT and NIRF imaging at 2 d after injection, and the feasibility of image-guided resection of intraperitoneal tumors was demonstrated in this model.Dual-labeled (111)In-DTPA-D2B-IRDye800CW enables specific and sensitive detection of prostate cancer lesions in vivo with micro-SPECT/CT and NIRF imaging. In addition to preoperative micro-SPECT/CT imaging to detect tumors, NIRF imaging enables image-guided surgical resection. These preclinical findings warrant clinical studies with (111)In-DTPA-D2B-IRDye800CW to improve tumor detection and resection in prostate cancer patients

    Water bottle flipping physics

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    The water bottle flipping challenge consists of spinning a bottle, partially filled with water, and making it land upright. It is quite a striking phenomenon, since at first sight, it appears rather improbable that a tall rotating bottle could make such a stable landing. Here, we analyze the physics behind the water bottle flip, based on experiments and an analytical model that can be used in the classroom. Our measurements show that the angular velocity of the bottle decreases dramatically, enabling a nearly vertical descent and a successful landing. The reduced rotation is due to an increase in the moment of inertia, caused by the in-flight redistribution of the water mass along the bottle. Experimental and analytical results are compared quantitatively, and we demonstrate how to optimize the chances for a successful landing.</p

    Measuring attitude toward theistic faith : assessing the Astley-Francis Scale among Christian, Muslim and secular youth in England

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    Empirical research within the social scientific study of religion in general and within the psychology of religion in particular remains very conscious of the complex nature of its subject matter. Empirical research in this field needs to take cognisance of the many forms in which religion is expressed (say, Buddhism, Christianity, Hinduism, Islam, Judaism, and Sikhism) and the many facets within the forms (say, beliefs, behaviours and affiliation). Working in the 1970s, Francis (1978a; 1978b) advanced the view that the attitudinal dimension of religion offered a particularly fruitful basis for coordinating empirical enquiry into the correlates, antecedents and consequences of religiosity across the life span

    Development of an analogue optical link for the front-end read-out of the ATLAS electromagnetic calorimeter

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    We have developed an analogue optical data transmission system intended to meet the read-out requirements of the ATLAS liquid argon electromagnetic calorimeter. Eight-way demonstrators have been built and tested. The link uses arrays of VCSEL diodes as the optical emitters, coupled to a 70 m long fibre ribbon to simulate the distance between the detector and the control room. The receiver is based around a custom-designed PIN photodiode array. We describe here the final results of laboratory tests on a demonstrator, laying stress on the VCSEL-to-fibre coupling issues, and the overall performance of the full link. A 9-bit dynamic range is achieved, with a 5on-linearity

    The Williams Scale of Attitude toward Paganism: development and application among British Pagans

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    This article builds on the tradition of attitudinal measures of religiosity established by Leslie Francis and colleagues with the Francis Scale of Attitude toward Christianity (and reflected in the Sahin-Francis Scale of Attitude toward Islam, the Katz-Francis Scale of Attitude toward Judaism, and the Santosh-Francis Scale of Attitude toward Hinduism) by introducing a new measure to assess the attitudinal disposition of Pagans. A battery of items was completed by 75 members of a Pagan Summer Camp. These items were reduced to produce a 21-item scale that measured aspects of Paganism concerned with: the God/Goddess, worshipping, prayer, and coven. The scale recorded an alpha coefficient of 0.93. Construct validity of the Williams Scale of Attitude toward Paganism was demonstrated by the clear association with measures of participation in private rituals

    The internal consistency reliability of the Santosh-Francis Scale of Attitude toward Hinduism among students in India

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    The Santosh–Francis Scale of Attitude toward Hinduism was originally developed and tested among Hindus in the UK as part of a programme designed to assess religious affect across faith traditions. The present study tests the internal consistency reliability and construct validity of the instrument among 149 students in Karnatak University Dharwad (74 males and 75 females), India. The data demonstrated an alpha coefficient of .90, suggesting a high level of internal consistency reliability and commending the instrument for further application within Hindu communities

    Are time-trends of smoking among pregnant immigrant women in Sweden determined by cultural or socioeconomic factors?

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    <p>Abstract</p> <p>Background</p> <p>The widening socioeconomic gap in smoking during pregnancy remains a challenge to the Swedish antenatal care services. However, the influence of cultural factors in explaining the socioeconomic differences in smoking during pregnancy is not clear among the immigrant women. The aim of this study was to investigate whether the development of smoking prevalence among pregnant immigrant women in Sweden followed the trajectory which could be expected from the stages of the global smoking epidemic model in the women's countries of origin, or not.</p> <p>Methods</p> <p>Delivery data on pregnancies in Sweden from 1982 to 2001 was collected from the Swedish Medical Birth Registry. From a total of 2,224,469 pregnant women during this period, all immigrant pregnant women (n = 234,731) were selected to this study. A logistic regression analysis and attributable fraction were used to investigate the association between smoking during pregnancy and the socioeconomic differences among immigrant women.</p> <p>Results</p> <p>Overall, the prevalence of smoking among pregnant immigrant women decreased from 30.3% in 1982 to 11.0% in 2001, albeit with remarkable differences between educational levels and country of origin. The greatest decline of absolute prevalence was recorded among low educated women (27,9%) and among other Nordic countries (17,9%). In relative terms, smoking inequalities increased between educational levels regardless of country of origin. The odds ratios for low educational level for women from other Nordic countries increased from 4.9 (95% CI 4.4-5.4) in 1982 to 13.4 (95% CI 11.2-16.2) in 2001, as compared to women with high education in the same group. Further, the total attributable fraction for educational difference increased from 55% in 1982 to 62% in 2001, demonstrating the strong effect of educational attainment.</p> <p>Conclusions</p> <p>Our hypothesis that the socioeconomic time trend of smoking based on the stage of the world wide tobacco epidemic model related to country of origin of the immigrant women was not supported by our analyses. Our findings does not support a call for specific "culture sensitive" antismoking policies or interventions in Sweden or similar countries, but reinforce the existing evidence with a focus on women with a low educational level, regardless of cultural background.</p

    The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial

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    \ua9 2023, The Author(s).BRAF genomic alterations are the most common oncogenic drivers in pediatric low-grade glioma (pLGG). Arm 1 (n = 77) of the ongoing phase 2 FIREFLY-1 (PNOC026) trial investigated the efficacy of the oral, selective, central nervous system–penetrant, type II RAF inhibitor tovorafenib (420 mg m−2 once weekly; 600 mg maximum) in patients with BRAF-altered, relapsed/refractory pLGG. Arm 2 (n = 60) is an extension cohort, which provided treatment access for patients with RAF-altered pLGG after arm 1 closure. Based on independent review, according to Response Assessment in Neuro-Oncology High-Grade Glioma (RANO-HGG) criteria, the overall response rate (ORR) of 67% met the arm 1 prespecified primary endpoint; median duration of response (DOR) was 16.6 months; and median time to response (TTR) was 3.0 months (secondary endpoints). Other select arm 1 secondary endpoints included ORR, DOR and TTR as assessed by Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO) criteria and safety (assessed in all treated patients and the primary endpoint for arm 2, n = 137). The ORR according to RAPNO criteria (including minor responses) was 51%; median DOR was 13.8 months; and median TTR was 5.3 months. The most common treatment-related adverse events (TRAEs) were hair color changes (76%), elevated creatine phosphokinase (56%) and anemia (49%). Grade ≄3 TRAEs occurred in 42% of patients. Nine (7%) patients had TRAEs leading to discontinuation of tovorafenib. These data indicate that tovorafenib could be an effective therapy for BRAF-altered, relapsed/refractory pLGG. ClinicalTrials.gov registration: NCT04775485

    Radioimmunotherapy Improves Survival of Rats with Microscopic Liver Metastases of Colorectal Origin

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    BACKGROUND: Half of the patients with colorectal cancer develop liver metastases during the course of their disease. The aim of the present study was to assess the efficacy of radioimmunotherapy (RIT) with a radiolabeled monoclonal antibody (mAb) to treat experimental colorectal liver metastases. METHODS: Male Wag/Rij rats underwent a minilaparotomy with intraportal injection of 1 x 10(6) CC531 tumor cells. The biodistribution of (111)In-labeled MG1, 1 day after intravenous administration, was determined in vivo and compared with that of an isotype-matched control antibody (UPC-10). The maximal tolerated dose (MTD) of (177)Lu-labeled MG1 was determined and the therapeutic efficacy of (177)Lu-MG1 at MTD was compared with that of (177)Lu-UPC-10 and saline only. RIT was administered either at the day of tumor inoculation or 14 days after tumor inoculation. Primary endpoint was survival. RESULTS: (111)In-MG1 preferentially accumulated in CC531 liver tumors (9.2 +/- 3.7%ID/g), whereas (111)In-UPC-10 did not (0.8 +/- 0.1%ID/g). The MTD of (177)Lu-MG1 was 400 MBq/kg body weight. Both the administration of (177)Lu-MG1 and (177)Lu-UPC-10 had no side-effects except a transient decrease in body weight. The survival curves of the group that received (177)Lu-UPC-10 and the group that received saline only did not differ (P = 0.407). Administration of (177)Lu-MG1 RIT immediately after surgery improved survival significantly compared with administration of (177)Lu-UPC-10 (P = 0.009) whereas delayed treatment did not (P = 0.940). CONCLUSION: This study provides proof of principle that RIT can be an effective treatment modality for microscopic liver metastases, whereas RIT is not effective in larger tumors

    Durable response with single-agent acalabrutinib in patients with relapsed or refractory mantle cell lymphoma

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    Bruton tyrosine kinase (BTK) inhibitors have greatly improved the spectrum of treatment options in mantle cell lymphoma (MCL) [1–4]. Acalabrutinib is a highly selective, orally administered, and potent BTK inhibitor with limited off-target activity [5]. Acalabrutinib was approved in 2017 by the US Food and Drug Administration for the treatment of relapsed/refractory MCL based on clinical data from the open-label, multicenter, phase 2 ACE-LY-004 study of acalabrutinib 100 mg twice daily [1]. Here, we present updated results from the ACE-LY-004 study after a median 26-month follow-up. Eligibility criteria and study design were published previously (Supplementary methods) [1]. Analysis of minimal residual disease (MRD) was conducted after complete response (CR) or partial response (PR) was achieved using the quantitative ClonoSEQ next-generation sequencing (5 × 10−6 ) assay (Adpative Biotechnologies, Seattle, WA, USA) in consenting patients with available paired archival tumor and whole blood samples. Data are updated as of February 12, 2018
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